Discussion
Key results:
Unlike previous epidemiological studies we did not find any evidence of
a significant difference in CRS disease status between active smokers
and non-smokers (p=0.5938). The lower number of active smokers observed
in both CRS subgroups may in part be a consequence of the higher
percentage of patients with concomitant asthma diagnosis as outlined in
Table 1. Active smoking appears however to have a significant impact on
quality of life in both CRSsNP and CRSwNP+ phenotypes although the
underlying mechanism remains debated in the common literature.
Multivariable analysis has shown that the higher SNOT-22 scores
demonstrated in CRS smokers remains significant even after adjusting for
age, sex and asthma diagnosis (Table 4). The Minimal Clinically
Importance Difference (MCID) value for SNOT-22 is 8.9, this being the
smallest change in treatment outcome that an individual patient would
term meaningful. Although it does not necessarily follow that smoking
negates the effect of treatment, the mean higher SNOT-22 score
(>10) in smokers underlies the significant impact of
smoking on overall symptom burden.
There was also no strong demonstrable evidence that active smoking
increases the likelihood of need for revision sinus surgery although
analysis of a larger cohort with standardised operative technique would
help clarify this further.
Interpretation:
CRES is the largest epidemiological study of CRS in the UK to date and
is the first study since the UK Sinonasal Audit to collect data on
patient reported symptoms and smoking status in the context of a
confirmed CRS diagnosis. The majority of previous population based
studies have reported positive associations between CRS prevalence and
tobacco
use.1,2The conclusions drawn by some of these studies are limited by their own
methodology, as unlike CRES they relied on self-reporting of CRS
diagnosis and hence are open to overestimation of true disease
prevalence. Analysing the UK CRES data, we have failed to demonstrate
any such positive association. We are not the first study to find a lack
of association with Pilan et al5 in Sao Paulo finding
no significant difference in CRS prevalence according to smoking status
(p = 0.43), total pack years (p = 0.26) or following exposure to second
hand smoke (p = 0.18). Min et al4 also confirmed CRS
diagnosis through physical examination but failed to find an association
between active and or former smoking status and CRS prevalence. A more
recent study by Lee et al21 reporting on data from the
Korean Health population survey (KNHANES) found an increased CRS among
active smokers however on multivariable analysis that there was no
overall significant difference between CRS prevalence and the patients
smoking status in those patients aged 40 years and below. They did
however note a similar finding to that recorded in the European
GA2LEN1 study that the number of
years smoked is significantly associated with CRS prevalence (increasing
by 1.5% for every year in total smoking period).
Some studies have suggested an increasing prevalence of CRS with total
number of years smoked.1,21 The results from Caminha
et al22 are however contradictory, finding on
multivariable analysis that Chronic Obstructive Pulmonary Disease (COPD)
incidence and hence a likely surrogate for greater smoking history was
not associated with a higher prevalence of rhinosinusitis symptoms.
Lachanas et al23 previously demonstrated that within a
general ‘non-CRS’ population, smokers have higher SNOT-22 scores
compared to non-smokers. It is clear from the CRES data that similarly
all active smokers (both active CRS and control patients) had average
higher SNOT-22 scores, although this was only statistically significant
for active smokers with confirmed CRS (Table 3). This adds some weight
to the argument that tobacco smoke may have an adverse effect on nasal
outcome measures independent to whether the patient has underlying CRS.
This finding has potential implications for epidemiological studies that
rely on CRS self-reporting or questionnaire-based assessments without
concurrent endoscopic CRS confirmation. These studies are vulnerable to
overestimating CRS complaints within the smoking population as smokers
appear more likely to have QOL nasal complaints and may perceive this
incorrectly as CRS.
Revision sinus surgery rates remain high in the CRS population,
evidenced from the National sinonasal audit five year follow up which
demonstrated increasing revision rates, reaching 19.1% at 5 years;
greatest in those patient with nasal polyps
(20.6%)24.
Previous CRES analysis demonstrated that 45% of CRS patients reported
some form of surgical procedure whilst multiple surgical procedures were
reported in 4% of CRSsNP patients and 23% of CRSwNP+
patients.25Interestingly the CRES smoking cohort reported lower numbers of surgical
interventions compared to non smokers (Table 5) and analysis failed to
find a statistical difference between smoking status and multiple
surgeries. These results suggest active smoking may not be a significant
risk factor for requiring multiple surgeries, however given the nature
of data collection and the low comparative number of smokers versus non
smokers this may not be truly representative. There are however multiple
variables that may contribute to the number of operations a patient
undergoes including the level of surgeon experience and selection bias
on whom to operate in which being an active smoker could play a negative
factor.
Previous studies have assessed the consequence of tobacco use on symptom
control and rates of revision surgery. Wu et al26analysed revision sinus surgery rates in patients with CRSwNP and found
on multivariable analysis that smokers had a significantly shorter time
period (median 2.82 vs. 4.31 years) before further revision surgery was
deemed
necessary.
A recent literature review by Reh at al27 reported
conflicting evidence with respect to surgical outcomes and smoking,
whilst earlier studies tended to demonstrate a deleterious effect more
recent prospective studies have failed to find an similar
association.
These conflicting literature findings may in part be accounted for by
differences in surgical intervention (e.g. polypectomy alone versus full
clearance FESS) and by evolving changes in technique and instrumentation
over the years. Interestingly Rudmik et al28 in their
prospective study reported that active smokers with recalcitrant disease
can experience similar benefits and improvement in quality of life
scores following endoscopic sinus surgery as their non-smoking peers.
There remains however a lack of studies looking at large numbers of
high-volume smokers which may help to clarify this association further.
The CRES analysis has demonstrated a higher symptom burden in active
smokers, with a mean difference in SNOT 22 scores greater than the MCID.
As an observational study we are limited in our conclusions; however our
failure to demonstrate an association between active smoking and higher
reports of revision surgery would align with recent prospective studies
concluding that surgery can be effective in smokers and should be
considered as a treatment option.
Limitations
The CRES study design has certain limitations, firstly the data was
self-reported and may therefore predispose to recall bias. Secondly the
study only included one specific question related to current tobacco
smoking, allowing us to determine whether the patient was an active
smoker and if they were a mild to heavy user. The selected question did
not identify whether patients were ex-smokers and did not seek to
quantify ‘pack year’ history nor did it enquire as to the presence of
other tobacco users in the household. We are therefore unable to
adequately comment on whether smoking is an independent risk factor for
developing CRS or comment on the possible role of second-hand smoke
exposure in CRS prevalence. The degree of tobacco use was not evenly
distributed amongst the CRES cohort with only 6-7% of patients reported
smoking heavily (>20 tobacco products a day). The data must
also be interpreted considering associated reporting bias relating to
the quantity people reported smoking, which could be an
under-representation. A further limitation of the study design meant
that data collection did not allow for calculation of total years
smoked, we are therefore unable to accurately comment on whether
prevalence of CRS in smokers appears dose dependent.
Generalisability
CRES is a cross sectional UK based study incorporating a variety of the
CRS population from across the country presenting to secondary care. The
CRES study does not necessarily capture the whole CRS spectrum as mild
sufferers may be managed by primary care alone and may therefore be
underrepresented. Further because of the multifactorial nature of CRS it
is difficult to assess the impact of one single factor on CRS
pathogenesis in isolation. In contrast to other studies, CRS was
diagnosed by ENT specialists according to accepted diagnostic guidelines
(EPOS 2012)16, other existing studies have relied on
self-diagnosis and or used different criteria making direct comparisons
with the existing literature more complicated.